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Introduction Inflammatory markers have long been observed in the brain, cerebrospinal fluid (CSF), and plasma of Alzheimer's disease (AD) patients, suggesting that inflammation contributes to AD and might be a therapeutic target. However, non‐steroidal anti‐inflammatory drug trials in AD and mild cognitive impairment (MCI) failed to show benefit. Our previous work seeking to understand why people with the inflammatory disease rheumatoid arthritis are protected from AD found that short‐term treatment of transgenic AD mice with the pro‐inflammatory cytokine granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) led to an increase in activated microglia, a 50% reduction in amyloid load, an increase in synaptic area, and improvement in spatial memory to normal. These results called into question the consensus view that inflammation is solely detrimental in AD. Here, we tested our hypothesis that modulation of the innate immune system might similarly be used to treat AD in humans by investigating the ability of GM‐CSF/sargramostim to safely ameliorate AD symptoms/pathology. Methods A randomized, double‐blind, placebo‐controlled trial was conducted in mild‐to‐moderate AD participants (NCT01409915). Treatments (20 participants/group) occurred 5 days/week for 3 weeks plus two follow‐up (FU) visits (FU1 at 45 days and FU2 at 90 days) with neurological, neuropsychological, blood biomarker, and imaging assessments. Results Sargramostim treatment expectedly changed innate immune system markers, with no drug‐related serious adverse events or amyloid‐related imaging abnormalities. At end of treatment (EOT), the Mini‐Mental State Examination score of the sargramostim group increased compared to baseline (P = .0074) and compared to placebo (P = .0370); the treatment effect persisted at FU1 (P = .0272). Plasma markers of amyloid beta (Aβ40 [decreased in AD]) increased 10% (P = .0105); plasma markers of neurodegeneration (total tau and UCH‐L1) decreased 24% (P = .0174) and 42% (P = .0019), respectively, after sargramostim treatment compared to placebo. Discussion The innate immune system is a viable target for therapeutic intervention in AD. An extended treatment trial testing the long‐term safety and efficacy of GM‐CSF/sargramostim in AD is warranted.

Living amphibians (Lissamphibia) include frogs and salamanders (Batrachia) and the limbless worm-like caecilians (Gymnophiona). The estimated Palaeozoic era gymnophionan–batrachian molecular divergence 1 suggests a major gap in the record of crown lissamphibians prior to their earliest fossil occurrences in the Triassic period 2 – 6 . Recent studies find a monophyletic Batrachia within dissorophoid temnospondyls 7 – 10 , but the absence of pre-Jurassic period caecilian fossils 11 , 12 has made their relationships to batrachians and affinities to Palaeozoic tetrapods controversial 1 , 8 , 13 , 14 . Here we report the geologically oldest stem caecilian—a crown lissamphibian from the Late Triassic epoch of Arizona, USA—extending the caecilian record by around 35 million years. These fossils illuminate the tempo and mode of early caecilian morphological and functional evolution, demonstrating a delayed acquisition of musculoskeletal features associated with fossoriality in living caecilians, including the dual jaw closure mechanism 15 , 16 , reduced orbits 17 and the tentacular organ 18 . The provenance of these fossils suggests a Pangaean equatorial origin for caecilians, implying that living caecilian biogeography reflects conserved aspects of caecilian function and physiology 19 , in combination with vicariance patterns driven by plate tectonics 20 . These fossils reveal a combination of features that is unique to caecilians alongside features that are shared with batrachian and dissorophoid temnospondyls, providing new and compelling evidence supporting a single origin of living amphibians within dissorophoid temnospondyls. Analysis of fossils of the oldest known caecilian provide insights into the origin and morphological and functional evolution of caecilians.

Pterosaurs were the first vertebrates to evolve powered flight 1 and comprised one of the main evolutionary radiations in terrestrial ecosystems of the Mesozoic era (approximately 252–66 million years ago), but their origin has remained an unresolved enigma in palaeontology since the nineteenth century 2 – 4 . These flying reptiles have been hypothesized to be the close relatives of a wide variety of reptilian clades, including dinosaur relatives 2 – 8 , and there is still a major morphological gap between those forms and the oldest, unambiguous pterosaurs from the Upper Triassic series. Here, using recent discoveries of well-preserved cranial remains, microcomputed tomography scans of fragile skull bones (jaws, skull roofs and braincases) and reliably associated postcrania, we demonstrate that lagerpetids—a group of cursorial, non-volant dinosaur precursors—are the sister group of pterosaurs, sharing numerous synapomorphies across the entire skeleton. This finding substantially shortens the temporal and morphological gap between the oldest pterosaurs and their closest relatives and simultaneously strengthens the evidence that pterosaurs belong to the avian line of archosaurs. Neuroanatomical features related to the enhanced sensory abilities of pterosaurs 9 are already present in lagerpetids, which indicates that these features evolved before flight. Our evidence illuminates the first steps of the assembly of the pterosaur body plan, whose conquest of aerial space represents a remarkable morphofunctional innovation in vertebrate evolution. Lagerpetids, bipedal archosaurs that are thought to be related to dinosaurs, are instead a sister group to pterosaurs, and although they have no obvious flight adaptations they share numerous synapomorphies with pterosaurs across the entire skeleton.

Dinosaurs and pterosaurs have remarkable diversity and disparity through most of the Mesozoic Era 1 – 3 . Soon after their origins, these reptiles diversified into a number of long-lived lineages, evolved unprecedented ecologies (for example, flying, large herbivorous forms) and spread across Pangaea 4 , 5 . Recent discoveries of dinosaur and pterosaur precursors 6 – 10 demonstrated that these animals were also speciose and widespread, but those precursors have few if any well-preserved skulls, hands and associated skeletons 11 , 12 . Here we present a well-preserved partial skeleton (Upper Triassic, Brazil) of the new lagerpetid Venetoraptor gassenae gen. et sp. nov. that offers a more comprehensive look into the skull and ecology of one of these precursors. Its skull has a sharp, raptorial-like beak, preceding that of dinosaurs by around 80 million years, and a large hand with long, trenchant claws that firmly establishes the loss of obligatory quadrupedalism in these precursor lineages. Combining anatomical information of the new species with other dinosaur and pterosaur precursors shows that morphological disparity of precursors resembles that of Triassic pterosaurs and exceeds that of Triassic dinosaurs. Thus, the ‘success’ of pterosaurs and dinosaurs was a result of differential survival among a broader pool of ecomorphological variation. Our results show that the morphological diversity of ornithodirans started to flourish among early-diverging lineages and not only after the origins of dinosaurs and pterosaurs. A well-preserved partial skeleton (Upper Triassic, Brazil) of the new lagerpetid Venetoraptor gassenae gen. et sp. nov. offers a more comprehensive look into the skull and ecology of dinosaur and pterosaur precursors.

Reptile feeding strategies encompass a wide variety of diets and accompanying diversity in methods for subduing prey. One such strategy, the use of venom for prey capture, is found in living reptile clades like helodermatid (beaded) lizards and some groups of snakes, and venom secreting glands are also present in some monitor lizards and iguanians. The fossil record of some of these groups shows strong evidence for venom use, and this feeding strategy also has been hypothesized for a variety of extinct reptiles ( e.g ., archosauromorphs, anguimorphs, and a sphenodontian). However, evidence of systems for venom delivery in extinct groups and its evolutionary origins has been scarce, especially when based on more than isolated teeth. Here, we describe a potentially venomous new reptile, Microzemiotes sonselaensis gen. et sp. nov., from a partial left dentary recovered from the Sonsela Member of the Chinle Formation (middle Norian, Upper Triassic) of northeastern Arizona, U.S.A. The three dentary teeth have apices that are distally reclined relative to their bases and the tip of the posteriormost tooth curves mesially. The teeth show subthecodont implantation and are interspaced by empty sockets that terminate above the Meckelian canal, which is dorsoventrally expanded posteriorly. Replacement tooth sockets are positioned distolingually to the active teeth as in varanid-like replacement. We identify this new specimen as a diapsid reptile based on its monocuspid teeth that lack carinae and serrations. A more exclusive phylogenetic position within Diapsida is not well supported and remains uncertain. Several features of this new taxon, such as the presence of an intramandibular septum, are shared with some anguimorph squamates; however, these likely evolved independently. The teeth of the new taxon are distinctively marked by external grooves that occur on the entire length of the crown on the labial and lingual sides, as seen in the teeth of living beaded lizards. If these grooves are functionally similar to those of beaded lizards, which use the grooves to deliver venom, this new taxon represents the oldest known reptile where venom-conducting teeth are preserved within a jaw. The teeth of the new species are anatomically distinct from and ~10x smaller than those of the only other known Late Triassic hypothesized venomous reptile, Uatchitodon , supporting venom use across multiple groups of different body size classes. This new species represents the third Late Triassic reptile species to possibly have used envenomation as a feeding (and/or defensive) strategy, adding to the small number of venomous reptiles known from the Mesozoic Era.

Dramatic early Cenozoic climatic shifts resulted in faunal reorganization on a global scale. Among vertebrates, multiple groups of mammals (e.g., adapiform and omomyiform primates, mesonychids, taeniodonts, dichobunid artiodactyls) are well known from the Western Interior of North America in the warm, greenhouse conditions of the early Eocene, but a dramatic drop in the diversity of these groups, along with the introduction of more dry-tolerant taxa, occurred near the Eocene–Oligocene boundary. Crocodyliforms underwent a striking loss of diversity at this time as well. Pre-Uintan crocodyliform assemblages in the central Western Interior are characterized by multiple taxa, whereas Chadronian assemblages are depauperate with only Alligator prenasalis previously known. Crocodyliform diversity through the intervening Uintan and Duchesnean is not well understood. The middle Eocene Devil’s Graveyard Formation (DGF) of southwest Texas provides new data from southern latitudes during that crucial period. A new specimen from the middle member of the DGF (late Uintan–Duchesnean) is the most complete cranial material of an alligatorid known from Paleogene deposits outside the Western Interior. We identify this specimen as a caimanine based on notched descending laminae of the pterygoids posterior to the choanae and long descending processes of the exoccipitals that are in contact with the basioccipital tubera. Unlike Eocaiman cavernensis , the anterior palatine process is rounded rather than quadrangular. The relationships and age of this new taxon support the hypothesis that the modern distribution of caimanines represents a contraction of a more expansive early Cenozoic distribution. We hypothesize that the range of caimanines tracked shifting warm, humid climatic conditions that contracted latitudinally toward the hothouse-icehouse transition later in the Eocene.

Introduction Hispanics/Latinos (H/Ls) are significantly underrepresented in Alzheimer's disease (AD) research participant samples. This exclusion limits our interpretation of research findings and understanding of the causes of brain health disparities. The Engaging Communities of Hispanics/Latinos for Aging Research (ECHAR) Network was created to engage, educate, and motivate H/Ls for participation in brain aging research by addressing several barriers to inclusion, including health literacy and AD‐related communication. Methods We used a novel community‐engaged method—Boot Camp Translation (BCT)—to translate medical jargon into action‐based, community‐relevant messages. H/L community members (n = 39) were recruited from three cities to work with local research teams and co‐develop culturally responsive AD‐related messaging. BCT meetings leveraged various techniques to identify key messages, the target audience for the messages, and methods to disseminate these messages. Themes were constructed collaboratively between BCT facilitators and community members as the group iteratively refined the conceptual framework and language for the main messages, with the goal to make AD messaging accessible for H/L community members. Results H/L community members showed significant improvements in subjective understanding (Cohen's d = 0.75; P < 0.001) and objective knowledge of Alzheimer's disease (Cohen's d = 0.79; P < 0.001) at BCT completion. H/L community members identified key messages that converged for all three cities. These were related to reducing stigma, emphasizing brain health and risk mitigation, and acknowledging the impact of AD on multi‐generational families/households. Participants also recommended sharing these messages with H/Ls across the lifespan using multi‐media avenues. Discussion The collaborative efforts identified culturally responsive and community‐relevant messaging that may help address health literacy barriers contributing to AD‐related disparities in H/L communities. HIGHLIGHTS Hispanics/Latinos are underrepresented in Alzheimer's disease and related dementias (ADRD) research despite increased risk. Limited ADRD health literacy may act as a recruitment barrier. Boot Camp Translation (BCT) is a process that targets health communication. We carried out BCT in three cities to co‐develop ADRD messaging. Results highlight regional similarities and differences in ADRD communication.

The shift to a cooler and drier climate through the Paleogene has been interpreted as the driver for changes in diversity and biogeographic distributions among mammalian taxa during the Eocene, leading to hypotheses of continued tropical climatic refugia in West Texas through the middle and late Eocene. However, the presence of ectothermic reptiles during that time has not been documented in detail and would potentially provide additional climatic indicators. We provide the first description of the herpetofauna from the Devil's Graveyard Formation (DGF), West Texas, the southernmost, wellsampled middle Eocene basin in North America. Specimens are derived from beds correlated with the Ui3 biochron of the late Uintan North American Land Mammal ‘Age’ (~45–40 Ma). We report the first amphisbaenians known from Texas, expanding our spatial and climatic understanding of rhineurid distribution, as well as the first glyptosaurine anguimorphs and alethinophidian snakes from the Purple Bench assemblage. These new amphisbaenians preserve a jugal posteriorly enclosing the orbit and an extremely short retroarticular process and are recovered in a clade comprising †Spathorhynchus, †Dyticonastis, †Ototriton, and †Hyporhina. The documentation of the amphisbaenians and other squamates provides biogeographic range extensions of these taxa to West Texas. Despite suggestions that West Texas was a middle and late Eocene climatic refugium for mammals adapted to subtropical forested environments, rhineurid amphisbaenians show a wide range of temperature tolerances up to the beginning of the Neogene.